Structure of human annexin I: comparison of homology modelling and crystallographic experiment.
A model of domain II of annexin I has been built by homology modelling using an annexin V crystal structure as a template. The method used is based on that of Summers and Karplus (J Mol Biol (1989) 210, 785-811) and involves the calculation of torsion-angle rotational energy maps to position side chains. The RMS deviation of the backbone heavy atoms between the model and a crystal structure of annexin I is 1.1 A. Similarities and differences in the experimental and model-derived side-chain rotameric conformations and hydrogen-bonding interactions are examined. It is found that whereas many of the side chains are well positioned some of those placed using the 'entropy argument' in which the broadest of the available minima are preferred, are erroneous. The domain is subjected to molecular dynamics simulation in explicit solvent. The simulations are found to 'correct' some of the side-chain rotamer positions that were poorly placed in the homology modelling. Considerable helix instability is seen in the simulations, consistent with the requirement of domain interactions for the structural integrity of the protein.
Musat
G V
GV
Section de Biophysique des Protéines et des Membranes, DBCM, CEA-Saclay, Gif-sur-Yvette, France.
Neumann
J M
JM
Smith
J C
JC
Sanson
A
A
D000595:Amino Acid Sequence; D017305:Annexin A1 / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data
D017305:Annexin A1